DESCRIPTION: The medical misuse and non-medical use of prescription opioid analgesics is a significant problem in USA and its societal effects and cost have been well documented. The emergence of abuse deterrent opioid products into the marketplace is targeted to stem the advance of this complex problem. Although new abuse deterrent opioid products have been introduced which deter manipulation of the product for intravenous and intranasal routes of administration, none of the currently marketed abuse deterrent products address the most prevalent route of opioid misuse and abuse, excess oral consumption. The recent FDA guidance on abuse deterrent opioids clearly notes the lack of an abuse deterrent technology to deter excess oral consumption. Acura Pharmaceuticals Inc. (Acura) is a small specialty pharmaceutical company focused on the development and commercialization of abuse deterrent products to deter medication abuse and misuse. Acura's Aversion(R) technology is contained in Pfizer's Oxecta immediate release oxycodone tablets, where intranasal and intravenous mechanisms are employed. Acura is now actively involved in developing a technology that will deter the misuse and abuse of opioid tablets when excess intact tablets are ingested. A self-regulating dose concept for an immediate release, opioid tablet with features to limit the release of opioid when excess tablets are swallowed, will be developed. In this concept, an opioid matrix particle is formed and mixed with buffering and antacid ingredients to comprise a tablet. Buffer/antacid levels per opioid dose are selected to only partially neutralize gastric acid such that the stomach remains relatively acidic (pH < 4) and the opioid matrix releases the opioid for absorption. However, when excess doses are ingested, buffer/antacid quantities are sufficient to neutralize gastric acid and elevate stomach pH (greater than or equal to pH 4). Under these conditions, the release of opioid would be slowed or limited as the high gastric pH environment is unfavorable for release from the opioid matrix. A demonstration self-regulating product using alprazolam, a benzodiazepine, has been developed. All ingredients used in this product are FDA approved at appropriate levels. In-vitro release of a single dose shows an immediate alprazolam release but when multiple doses are tested the in-vitro release is delayed such that the time to peak release is significantly lengthened compared to alprazolam tablets without self-regulation. This concept would be expected to show similar results in-vivo, where a reduced rate of rise from excess oral consumption would provide a significant safety factor from overdosing and to deter drug seeking behavior by lessening the potential high. Based on this concept, Acura plans to complete product and clinical development for a self-regulating hydromorphone HCl tablet and to file a 505(b)2 NDA for product approval.